Productivity & GMP

PREFORMULATION AND PRODUCTION MANAGEMENT
PRODUCTIVITY AND GMP CONSIDERATIONS
Seminar on,
PRODUCTIVITY
&
GMP CONSIDERATIONS
PRODUCITVITY
Definition
Reasons to Increase Productivity
How to Increase Productivity
Economic Growth and Productivity
Main Processes of A Company From Which Productivity Is
Created and Distributed
Measuring An Interpreting Partial Productivity
Other Aspects of Productivity
PRODUCTIVITY
DEFINITION:
Nagaraja y s Dept.of Pharmaceutics

Productivity may be defined as the ratio of output to input.

Output - means the amount or the no. of units produced.
Input
- are various resources like Land and building, equipment
and machinery, material, labour etc.

In abroad sense, productivity is considered for the entire process,
while efficiency is referred to individual operation and machines.
REASONS TO INCREASE THE PRODUCTIVITY:
It is always necessary to increase productivity continuously for various
reasons.
For management: To sell more and earn good profits.

To clear the debts or loans acquired from different sources
To establish better position in the market.
For workers.
To get higher wages and standards of living.
To work in better working conditions.
To attain job security and satisfaction.
For customers.
To obtain articles at reduced price.

HOW TO INCREASE THE PRODUCTIVITY:

The resources should be utilized judiciously for increasing
productivity by;
Making proper use of raw materials and reducing the manufacturing
defects. This can be achieved by using the right process, right design
and right storage facilities.
Improving work study technique and training, so that labour can rise
to the occasion and give higher productivity.
Maintaining the equipment in good working condition and reducing
setup costs.
Adapting proper construction and layout.
Shortening the work for 3 or 4 day/week and lengthening the shifts
to 10 to 13 hrs/day.
Keeping wages more closely to output and providing merit awards.
Developing and utilizing Standard time in service industries.
Improving communication to encourage everyone to work towards
the same desired objectives.
Redesigning the new technologies also increases the productivity.
Cycle time reduction.

Productivity can be considered as increased, if more products are

produced from the same amount of resources.
ECONOMIC GROWTH AND PRODUCTIVITY:
Economic activity can be identified with production and
consumption. Production is a process of combining various
immaterial and material inputs of production so as to produce tools
for consumption.
By the help of production function, it is possible to describe simply
the mechanisms of economic growth.
Economic growth is created by two components.
a) Increase in production input.
b) Increase in productivity.

The figure represents an economic growth process

Reviewing the process in the subsequent years one and two,
production has increased from value T1 to T2.
Both years can be described by a graph of production functions,
each function being named after the respective no. of the year
1&2.
Two components are distinguishable in the output increase.
i.e.

a) The growth caused by an increase in production input.

b) The growth caused by an increase in productivity.
Characteristic of the growth effected by an input
increase is that the relation between output and input remains

unchanged.
An increase in productivity is characterized by a
shift of the production function and a consequent change to the

output and input relation.
The formula of total productivity is normally written
as follows.
Total Productivity = Output quality and quantity

Input quality and quantity
According to this formula, changes in input and
output have to be measured inclusive of both quantitative and

qualitative changes.
MAIN
PROCESSES
OF
COMPANY
FROM
WHICH
PRODUCTIVITY IS CREATED AND DISTRIBUTED:

A company can be divided into sub processes in different ways. Yet,
the following are identified as the main process.
a) Real Process.
b) Income Distribution process.

c) Production Process.
d) Monetary Process.
e) Market Value Process.
Productivity is created in the real process, productivity gains are
distributed in the income distribution process and these two processes
together constitute the production process.
a) REAL PROCESS:
Real process generates the production output and it can be
described by means of the production function.
It refers to a series of events in which production inputs of
different quality and quantity are combined into products of
different quality and quantity.
Products can be a physical goods, immaterial services and most
often combinations of both.
b) INCOME DISTRIBUTION PROCESS:
It refers to a series of events in which the unit prices of constant
quality products and inputs alter causing a change in income
distribution among those participating in the exchange.

The magnitude of the change in income distribution is directly

proportional to the change in prices of the output and inputs and
to their quantities.
Productivity gains are distributed, for e.g. to costumers as lower
product prices or to staff as higher pay.
c) THE PRODUCTION PROCESS:
The production process of consist of the real process and the
income distribution process. A result and criterion of success of
the production process is profitability.
Factors describing the production process are the components
of profitability i.e. returns and costs.
They differ from the factors of the real process in that the
components of profitably are given at nominal prices where as in
the real process the factors are at fixed prices.
d) MONETARY PROCESS:
It refers to events related to financing the business.
e) MARKET VALUE PROCESS:
It refers to a series of events in which investors determine the
market value of the company in the investment markets.

MEASURING AND INTERPRITING PARTIAL PRODUCTIVITY:

The term of partial productivity illustrates well the fact that total
productivity is only measured partially or approximately.
Measurement of partial productivity refers to the measurement
solutions which do not meet the requirements of total
productivity measurement.
The solutions are,
i. Single Factor Productivity: - it refers to the measurement
of productivity that is ratio of output and one input factor.
ii. Value Added Productivity:-sometimes it is practicable to
employ the value added as output and Productivity
measured in this way is called as value added productivity.
iii. Unit Cost Productivity:- Productivity can be examined in
cost accounting using unit costs.
iv.
Efficiency Ratios:- which tell something

about the ratio between the value produced and sacrifices
made for it, are available in large no.
v. Managerial Control Ratio System:- these systems are

composed of single measures which are interpreted in
parallel with other measures related to the subjects.
The measures of partial productivity are,

1) Physical Measures.
2) Nominal Price Value Measures.
3) Fixed Price Value Measures.
VARIABLE TO BE
VARIABLE TO BE
MEASURED
EXCLUDED
Quality and
TYPE OF MEASURE
Physical
Fixed Price Value
Quantity
Quantity and Quality
Distribution
Distribution
Quantity, Quality and

Nominal Price Value
None
Distribution
The table above is complied to compare the basic types of measurement.
OTHER ASPECTS OF PRODUCTIVITY:

Productivity studies: Analyze technical process and
engineering relationships such as how much of an output
can be produced in a specified period of time.
Increase in productivity: Influence society more broadly, by
improving living standards and creating income.
They are central to the process generating economic growth
and capital accumulation.

Labour productivity: Average products of labour (average

output per worker or per worker hour, and output which
could be measured in physical terms and in price terms).
CONTENTS
GOOD MANUFACTURING PRACTICES
Introduction
Definition
Objectives
Various Aspects of GMP
Premises
Equipment and Utensils
Personnel
Sanitation
Ancillary Area
Medical Devices / Services
Raw Materials
Manufacturers
Reprocessing and Recovery
Packaging and Labeling
Storage
Sterile Products
Considerations for Finished Products

Quality Control System

Quality Assurance
Documentation
Validation
Return Goods
Product Recall
Training
Audit / PAI
GOOD MANUFACTURING PRACTICE
INTRODUCTION
The first cGMP regulations were issued in 1963, one year after the
enactment of the 1962 Kefauver- Harris drug amendments.
Although it took about 8 years to revise them, that is in 1971 and
they are in no way stagnant.
The word current, suggest that they are dynamic and
Regulatory agency constantly updates and maintains them in
relation to the current state of the art and science of drug
manufacturing practices in the industry.
Next revision of the cGMP took place in 1978 and these are in effect
at present.

GMP regulations were introduced in the form of amended schedulem in 1988.

The Schedule-M has again been amended in-2001, in a major way
by the drug and cosmetics rules, 2001 dec and embraces rules 71,
74, 76 and 78 under the drugs and cosmetics rules 1945.
GMP is also the part of Q.A. that ensures products are consistently
produced and controlled to the quality standards appropriate to their
intended use & legal requirements.
GMP is to diminish the risks which are inherent in any
pharmaceutical products.
DEFINITION: cGMP is a regulation which provides for the methods
to be used in and the facilities or control to be used for
a) Manufacturing
b) Processing
c) Packaging
d) Holding a drug to assure that the drug meets the safety,
requirements of the federal food drug and cosmetic act and
also that the drug has the identity, strength, quality, purity
characteristics which it is represented to possess.
What does it mean to manufacturing pharmacist:

The requirement is broadly stated that it casts a tremendous

burden of proof on the FDA, especially in cases where there
arguable variables in methodology, procedure or equipment.
It also cost a heavy burden on the industrial pharmacist, however,

because it requires him to produce drug products by using
manufacturing practices that are both good and current.
In other words, he must keep up with advances and adopt those
that will increase assurance of drug integrity according to the
requirements of the Act.
All production personnel should understand GMP at least as it
applies to their particular area of responsibility and also to know
what an FDA inspector looks for.
OBJECTIVES:
The production process are clearly defined, systemically reviewed
and validated.
All the necessary facilities are provided.
Critical processing steps, key equipments and services are
validated.
Operators are trained to carry out procedure correctly.

Records of production, in-procces, final control and distribution

are maintained.
System is available to recall products.
Complaints are made to take in to consideration.\
THE VARIOUS ASPECTS OF GMP:
To achieve the objectives listed above each licensee shall evolve
methodology and procedure which should be documented and
kept for reference and inspection.
GMPS are mandatory & the compliance with them is a
prerequisite for the grant or renewal of a manufacturing license.
Following are the aspects which are considered in GMP.
1. PREMISES:
A.LOCATION AND SOURROUNDING:
The factory building for manufacture of drugs shall be situated &
shall have such measures to avoid risk of contamination from, open
sewage, drain, public lavoratory, and any other factory which
produce disagreeable or obnoxious odour, fumes, excessive soot,
dust, smoke, chemical or biological emissions.
B.BUILDING:

The premises used for manufacturing, processing, packing, labeling and

testing purpose shall be,
Compatible with other manufacturing operations that may be carried
out in the same or adjacent area or section.
Adequate working space should be provided to allow orderly &
logical placement of equipment, materials & movement of personnel
so as to avoid the risk of mix up, contamination & cross
contamination.
Designed, constructed, and maintained to prevent entry of insects,

pests, birds, vermins & rodents.
Shall be well lighted, effectively ventilated, with air controlled

facilities & may have proper air handling units to maintain
conditions including temperature & humidity as defined for the
relevant product & these areas shall be regularly monitored for
compliance with required specifications.
Provided with drainage system, as specified for the various
categories of products, which shall be of adequate size & so
designed as to prevent back flow and/or prevent insects & rodents
entering the premises.

The walls and floor shall be free from crack and open joints &
permit easy cleaning, painting & disinfection.
C.WATER SYSTEM:
The water used should be pure and of drinkable quality.
There shall be validated system for treatment of water drawn from
own or any other source to render it potable as the case may be, so
as to produce purified water confirming to pharmacopoeial
specifications.
D.DISPOSAL OF WASTE:
The disposal of waste from the manufactory shall be in conformity
with the requirements of Environment Pollution Control Board.
Disposal methods vary considerably according to situation some are,
1) Return to donor or manufacturer.
2) Landfill i) waste immobilization:encapsulation.
ii) Waste immobilization: inertlization.
3) Sewer.
4) Burring in open containers.
5) Chemical decomposition.
2. EQUIPMENT AND UTENSILS:
A.DESIGN AND CONSTUCTION:

The equipment used in the manufacturing process must be of

appropriate design, adequate size and suitably located for its
intended use, cleaning, sanitization and maintenance.
The surface of the production equipment that comes in contact with
the raw material, intermediate or AIS should not be reactive,
additive or adsorptive to an extent that would affect the quality of
the product.
Any substances associated with operation of equipment such as
coolants, lubricants, heating fluids etc. should not alter quality.
Closed equipment should be used whenever appropriate. When open
equipment is used, appropriate precautions must be taken to
minimize the risk of contamination.
A set of current drawings must be maintained for equipment and
critical installations.
B.MAINTENANCE AND CLEANING:
Schedule and procedures must be established for the preventive
maintenance of equipment.
Written procedures must be established for the cleaning and its
subsequent release for use in manufacturing.

Equipments and utensils must be cleaned, stored and wherever

appropriate sanitized or sterilized to prevent contamination or carry
over.
Non dedicated equipment must be cleaned between productions of
different materials to prevent cross contamination.
C.CALIBRATION:
Control, weighing, measuring, monitoring and test equipment that is

critical for assuring the quality of the product must be calibrated.
Records of these calibrations must be maintained.
The instruments that do not meet calibration criteria must not be

used.
3. PERSONNEL:
A.PERSONNEL QUALIFICATION:
There should be an adequate no of personnel qualified by

appropriate education, training and/or experience to perform and
supervise the manufacturing aspects.
The responsibilities of all personnel engaged in the manufacturing

process must be specified in writing.

Training should be regularly conducted by qualified individuals and

should cover, at a minimum, the particular operations that the
employee performs and GMP as it relates to the employees
functions.
B.PERSONNEL HYGIENE:
Personnel should wear clothing suitable for manufacturing activity
with which they are involved. Additional protective apparel, such as
head, face, hand, and arm coverings. Should be worn when
necessary, to prevent contamination.
Personnel must avoid direct contact with intermediates or active
ingredients.
Smoking, eating, drinking, chewing, and storage of food must be
restricted to certain designated areas separate from manufacturing
area.
All personnel prior to employment and thereafter should be
Subjected to periodic medical check up and personnel suffering
from any infectious diseases or having open lesions on the exposed
surface of body should not engage in the activities that could result
in the compromising the quality of product.

The personnel handling beta-lactum antibiotic shall be tested for

penicillin sensitivity before employment and those handling sex
hormones, cytotoxic substances and other potent drugs shall be
periodically examined for adverse effects. These personnel should
be moved out of these sections (except in dedicated facilities), by
rotation, as a health safeguard.
All personnel prior to and during employment shall be trained in
practices which ensure personnel hygiene. Instructions to this effect
shall be displayed in change rooms and other strategic locations.
All personnel shall be instructed to report about their illness or
abnormal health condition to their immediate supervisor so that
appropriate action can be taken.
4. SANITATION:
The manufacturing area shall not be used for any other purpose.
Manufacturing premises shall be Maintained clean and in an orderly

manner, free from accumulated waste, dust, debris etc;

A routine sanitation Programme shall be drawn up and observed

which shall be properly
recorded and which shall indicate,
-Specific areas to be cleaned and cleaning intervals

-Cleaning procedures to be followed, including
equipment to be used for cleaning; and
-Personnel assigned to and responsible for cleaning
operation.
Records of compliance in respect of sanitization shall be
maintained for inspection.
5. ANCILLARY AREAS:
Rest and refreshment rooms shall be separate from other areas.
These areas shall not lead directly to the manufacturing and storage
areas.
Facilities for changing, storing clothes, washing and toilet purpose
shall be easily accessible and adequate for the no of users. Toilets,
separate for males and females, shall not be directly connected with
production or storage areas. There shall be written instructions for
cleaning and disinfection of such areas.
Maintenance workshops shall be separate and away from production
areas. Whenever spares, changed parts and tools are stored in the

production area, these shall be kept in dedicated rooms or lockers.

Tools and spare parts for use in sterile areas shall be disinfected
before these are carried inside the production area.
Areas housing animals shall be isolated from other areas.
6. MEDICAL DEVICES/ SERVICES:
The manufacturer shall provide,
Adequate facilities for first aid.
Medical examination of workers at the time of employment and
periodical check up thereafter once in a year, with particular
attention being devoted to freedom from infectious conditions.
Records thereof shall be maintained; and
Facilities for vaccination or other exigencies. The licensee shall
provide services of a qualified physician for assessing the health
status of all employees.
7. RAW MATERIAL:
Responsible person must keep an inventory of all raw materials to

be used and maintain records as per schedule U.
All incoming materials shall be purchased from approved sources

under valid purchase vouchers.

Identified and containers examined for integrity of package and

assigned control no.
If a single delivery of material is made up of different batches, each
batch shall be considered a separate batch for sampling, testing and
release.
Systemically sampled by Q.C. personnel.
There shall be adequate separate area for materials under test,

approved and rejected.
Stock rotation is on the basis of first in first out principle.

Conspicuously labeled indicating the name of the materials, control
no, name of the manufacturer and be specifically labeled under test
or approved or rejected.
8. MANUFACTURE:
A.PRODUCTION AREA:
The production area shall be designed to make production uni- flow

and with logical sequence of operations.
In order to avoid risk of cross-contamination, Separate dedicated

and self contained facilities shall be made available for the
production of sensitive products like penicillin or biological
preparations with live micro-organisms.seperate dedicated facilities

shall be provided for the manufacture of contamination causing and

potent drugs such as Beta lactum, sex hormones and cytotoxic
substances.
Working space should be adequate to permit orderly and logical
placement of equipment and materials and movement of personnel
to avoid cross-contamination and to minimize risk of omission or
wrong application of any manufacturing and control measures.
Pipe work, electrical fittings, ventilation openings, and similar
service lines shall be designed, fixed and constructed to avoid the
formation of recesses.
B.MANUFACTURING PROCEDURES:
Manufacture shall be carried out in accordance with master formula.
Critical steps in the process relating to selection, weighing, and
measuring of raw material addition during various stages shall be
validated.
Manufacture shall be supervised and performed by competent
persons.
During manufacture, Equipment, vessels and containers shall be

identified through proper labeling, that includes the name of the
product, batch no, batch size and stage of manufacture. Labels shall

be attached to all mechanical manufacturing equipment during their

operation with conspicuous labels bearing the name of the product
and batch no.
Daily activities shall be are recorded.
Products not prepared under aseptic conditions are required to be
free from pathogens like salmonella, E. coli, Pyocyanea, etc.
Sampling and testing in process materials and drug products shall be
carried out to monitor the product quality.
C.PRECAUTIONS AGAINST CONTAMINATIONS AND MIX UP:
The licensee shall prevent cross-contamination of drugs with sex
hormones, beta lactum antibiotics, and antineoplastic drugs by
appropriate methods, which may include Carrying out Production in segregated areas followed by appropriate
cleaning.
Using appropriate pressure differential in the processing area;
Provide appropriate air locks and exhausts
Designing sterile air systems for sterile products;
Using UV lamps.
Packaging line shall be independent and adequately segregated. It
shall be ensured that all left overs of the previous packaging

operations, including labels, cartons and caps are cleared before the
closing hours.
Line clearance shall be performed by appropriate checklist and
record.
Any necessary in process controls and environmental controls
should be carried out and recorded.
Individual containers of liquid orals, parenterals and ophthalmic
solutions shall be examined against black-white background fitting
with diffused light after filling to ensure freedom from
contamination with foreign suspended matter.
9. REPROCESSING AND RECOVERY:
If a product batch has to be reprocessed, return procedures shall be
established, authorized and recorded such reprocessing shall be
validated.
Recovery of the product residue may be carried out by incorporating
in subsequent batches of the product, if permitted in the master
farmula.Recovered material that will alter the quality of product
should not be
used

Limits, approved by the quality control, should be established for

the amount of recovered material which may be added to a
subsequent batches.
Batches incorporating residues should not be released until the
batches from which the residues originated have been tested and
found suitable for use.
An investigation shall be carried out in to the causes necessitating
reprocessing and corrective measures shall be taken.
10. PACKAGING AND LABELLING;
All containers and closures shall comply with pharmacopoeial
requirements. Suitable specifications, test methods, cleaning procedure and
sterilization procedure, when indicated, shall be used to assure that
containers, closures and other component parts of drugs packages, are
suitable and they are not reactive, additive, adsorptive or leach to an extent
that significantly will affect the quality or purity of drug.
Measure physical and chemical changes of all containers and

closures under extreme heat, moisture and light conditions.
Measure physical protection provided by containers.

Toxicity, compatibility and stability studies shall be carried out for

containers and closures.
Leakage test for ampoules, collapsible tubes, strip packs, pin holes
in strips should
be conducted
Written procedures shall be established for packaging and labeling.

Before entering in to packaging area, packaging line clearance shall
be checked.
Prior to issue, all labels for containers, cartons and boxes and all
circulars, inserts and leaflets shall be examined and released by
quality control personnel.
Prior to packaging and labeling of a given batch of drug it must be

ensured that the batch has been duly tested, approved and released
by the quality control personnel.
To prevent packaging and labeling errors, a known no of labeling

and packaging units are issued and if required coded.
Upon completion of packaging and labeling operation, comparison

shall be made between number of labeling and packaging units and
no of units labeled and packaged.
Unused coded and spoiled labels and packaging materials are
destroyed.

Records shall be maintained for each shipment received of each

packaging material indicating receipt, examination relating to testing
and whether approved or rejected.
11. STORAGE (WAREHOUSING AREA):
Materials should be handled and Stored in a manner to prevent

degradation, contamination, and cross contamination.
Materials should be stored under conditions for a specified period

that have no adverse effect on the quality.
Adequate areas shall be designed to allow sufficient and orderly
warehousing of various categories of materials and products like
starting and packaging materials, intermediates, bulk and finished
products, products in quarantine, released, rejected, returned, or
recalled, machine and equipment spare parts and change items. and
segregated areas shall be designed
This area shall be Clean, dry and maintained with acceptable

temperature limits, where special storage conditions are required
shall be provided, monitored and recorded. Proper racks, bin and
platforms shall be provided for the storage of materials.

Quarantine status if ensured by warehousing separate area shall be

provided and access to such areas shall be restricted to authorized
persons.
There shall be a Separate sampling area for active raw materials and
excipients. If sampling is performed in any other area, it shall be
conducted in such away as to prevent contamination, cross
contamination and mix up.
Segregation shall be provided for the storage of rejected, recalled or

retained products. Such areas, materials and products shall be
suitably marked and secured.
Highly hazardous, poisonous and explosive materials such as
narcotic, psychotropic drugs and substances presenting potential
risks of abuse, fire or explosion shall be stored in safe and secure
areas and adequate fire protection measures shall be provided in
such areas.
Separate dispensing area for -lactum, sex hormones and cytotoxic
substances or any such special categories of products shall be
provided with proper supply of filtered air and suitable measures for
dust control to avoid contamination. Such areas shall be under
differential pressure.

Sampling and dispensing of sterile materials shall be conducted in a

specific condition (Grade A).
Rodent treatment should be done regularly and at least once in a
year and record maintained.
Storage Specification
Cold
Freezer
Cool
Room temperature
Warm
Excessive heat
12. STERILE PRODUCTS:
Temperature Conditions
Not to exceed 80C
-100 to -200C
80to 150C
150 to 300C
300 to 400C
Above 400C
Cleanup area is constructed to withstand moisture, steam and

detergents and is usually class 1, 00,000 clean area.
The ceiling Walls and floors should be constructed of

impervious material so that moisture will run off and not be held.
These areas should be exhausted adequately, so that the heat and

humidity will be removed for the comfort of personnel.
Precautions must be taken to prevent accumulation of dirt and the

growth of microorganisms because of the high humidity and heat.
Adequate sink and counter space must be provided.

Cabinets and counters should preferably be constructed of

stainless steel and hung from wall, so that there are no legs to
accumulate dirt where they rest on the floor.
All light fixtures, utility service lines and ventilation fixtures
should be recessed in walls to eliminate joints and other locations
for the accumulation of dirt.
Personnel entering the aseptic area should enter only through an
air lock.
They should be attired in sterile coveralls with sterile cloths,
sterile hats, masks, goggles and foot covers etc. in and out
movement rigidly be restricted during a filling operation.
To remove fine debris down to the submicron range, including

micro organisms, a HEPA filter, defined as at least 99.97%
efficient in removing partials of 0.3 micro meter size and larger
and composed of glass fibers and fillers or electrostatic
precipitators may be employed.
AIRBORNE PARTICULATE CLASSIFICATION FOR
MANUFACTURE OF STERULE PRODUCTS
Maximum No. Viable
Grade
Maximum No. of Permitted Particles Per Cubic
Microorganisms
Meter
Permitted Per Cubic

Meter

0.5-5 m
100 at rest &3500 (3520) in
> 5 m
operation
Nil (29)
<1
3500 (35,200)
Nil (293)
3,50,000 (3,52,000)
2,000 (2,900)
100
35,00,000 (35,20,000)
20,000 (29,300)
500
GRADES FOR ASCEPTIC PREPARATION

CLASS
100
( GRADE A & B)
10,000
( GRADE C)
1,00,000
( GRADE D)
TYPES OF OPERATIONS
ASEPTIC PREPARATION AND FILLING
(SHALL BE ACHIEVED BY PROVIDING LAF
MODULE)(MORE AIR CHANGES)
PREPARATION OF SOLUTION TO BE FILTERED
HANDLING OF COMPONENTS AFTER WASHING
TYPES OF OPERATIONS TO BE CARRIED OUT IN THE

VARIOUS GRADES FOR TERMINALLY STERILIZED
PRODUCTS
CLASS
TYPES OF OPERATIONS
100
FILLING OF PRODUCTS WHICH ARE USUALLY
(GRADE A & B)
10,000
AT RISK
FILLING AND SEALING, PREPARATION OF
( GRADE C)
SOLUTION. FILLING OF PRODUCTS WHICH ARE

USUALLY NOT AT RISK

1,00,000
( GRADE D)
FORM, FILL & SEAL
ENVIRONMENTAL MONITORING SCHEDULE

A) Particulate Monitoring In Air Monthly (6 monthly)
B) HEPA filter integrity testing (smoke testing) 6 monthly for LAF
used for aseptic operation (Yearly).
C) Air change rates 6 monthly
D) Air pressure differentials daily
E) Temperature and humidity daily
F) Microbiological monitoring by settle plates and/or swabs in aseptic
areas daily, and at decreased frequency in other areas.
13. CONSIDERATION FOR FINISHED PRODUCTS:
STORAGE
DISTRIBUTION
Records shall be maintained on the distribution of each batch
of a product in order to facilitate the recall of the batch if
necessary.

The authorities shall be promptly informed when one or more

batches are to be
withdrawn form sale or use because they
are defective.
COMPLAINTS AND PRODUCT DEFECTS
All complaints threof concerning product quality shall be
carefully received and recorded according to written
procedures.
Each complaint shall be Investigated and records of
investigation and subsequent action taken thereof shall be
maintained.
Reports of any hazardous reactions resulting from the use of a
drug along with comments and documents shall be reported
to the concerned authorities.
Manufacturer shall maintain written instructions of dealing
such complaints concerning the quality of product.
14. QUALITY CONTROL SYSTEMS:
Every manufacturing establishment shall have a quality control
department. This shall control all raw materials, monitor all in process
quality checks and control the quality and stability of finished product.

Adequate facilities, trained personnel and approved procedures

should be made available for inspecting and testing of starting and
packaging materials, intermediates, bulk and finished products and
also monitoring environmental conditions for GMP purpose.
Samples of all materials taken by qualified personnel by methods
approved by quality control.
Test methods are validated.
Adequate standards and reagents are maintained.
Sops shall be available sampling, inspecting and testing of all
materials.
No batch of Product is released for supply prior to certification by a
qualified pharmacist that it is in accordance with all legal
requirements.
Separate areas shall be provided each for physicochemical,
biological, microbiological or radio-isotope analysis. Separate air
handling units and other requirements shall be provided for
biological, microbiological and radio-isotope testing areas.
Pharmacopoeia, reference standards, spectra shall be available
Records maintained
15. QUALITY ASSURANCE:

This is wide ranging concept concerning all matters that individually or

collectively influence the quality of product. It is the totality of the
arrangements made with the object of ensuring that the products are of
the quality required for there intended use.
The system of quality assurance appropriate to the
manufacture of pharmaceutical products shall ensure that: The pharmaceutical products are designed and developed in a
way that takes account of the requirement of GMP, GLP and GCP.
Adequate arrangements are made for manufacture supply and use
of the correct starting and packaging materials.
Adequate controls on starting materials, intermediate products,
bulk products and other in process controls, calibrations and
validations are carried out.
The finished product is correctly processed and checked in
accordance with established procedures.
Pharmaceutical products are not released for sale or supply before
authorized person have certified that product comply with
requirements of label claim.
16. DOCUMENTATION:

Documentation is an essential part of quality assurance system and, as

such, shall be related to all aspects of GMP. Its aim is to define the
specifications for all materials, method of manufacture and control;
therefore it is defined as a method of preparing written material that gives
the complete description of process in terms of specifications, instructions,
controls etc.
Documents shall be designed, prepared, reviewed, and controlled
wherever applicable.
Documents shall be approved, signed and dated by authorized
persons.
Shall specify the title, nature and purpose. Any alteration made in
the entry of a document shall be signed and dated.
The Records shall be made or completed at the time of each
operation in such a way that all significant activities concerning
the manufacture of pharmaceutical products are traceable.
Records and associated SOPS shall be retained at least one

year after the expiry date of finished product.
A. MASTER FORMULA RECORDS:

Master formula records are defined as a written procedures that give
a complete description of all aspects of its manufacture, packing and

control with an intension to ensure the identity, strength, quality and purity
of each dosage unit through out its entire self life.
It shall give,
Patent or proprietary name, generic name, strength and dosage
form.
Description or identification of final container, packaging
material, labels and closures to be used.
The identify quality and quantity of each raw material to be used
irrespective of whether or not it appears in the finished product.
The permissible overage that may be included in a formulated
batch should be indicated.
A description of all vessels and equipment and the sizes used in
the process.
Manufacturing and control instructions along with parameters
for critical steps such as mixing, dry blending, sieving,
sterilizing the product etc.
Theoretical yield to be expected from the formulation at
different stages of manufacture and permissible yield limits.
The requirement of in process quality control tests and analysis
to be carried out.

B.BATCH MANUFACTURING RECORDS:

Batch manufacturing records are a detailed description of instructions,
specifications, procedure and controls for the production of a batch of drug
product.
It shall give,
Name of preparation, size and batch no.
Dates of different stages of manufacture.
Manufacturing details, including reference to the main equipment
used.
A record of in-process control followed and the results obtained.
Batch no. of each starting material.
Initials of operations and sign of the person responsible for the

manufacturing operations and the date of his sign.
All analytical records relating to the batch with the date and sign
of person responsible for the decision.
A decision for the release or rejection of batch.
C.RETENTION OF RECORDS AND REFERENCE SAMPLES:

Records and reference samples shall be retained at least for One

year after expiry or expected market life of product.
Reference Samples of starting materials and finished products

shall be of sufficient size to enable necessary analysis to be
carried out during the retention period and shall stored under
recommended conditions.
17. VALIDATION:
Validation is a establishing documented evidence, which provides high
degree of assurance that a specific process or equipment will consistently
produce a product meeting its predetermined specifications and quality
characteristics.
Validation studies shall be an essential part of GMP and shall be
conducted as per the predefined protocols. These shall include
validation of processing, testing and cleaning procedures.
Records of results and conclusions shall be prepared,
documented and maintained.

Processes and procedures shall be established on the basis of

validation study and undergo periodic revalidation to ensure that
they remain capable of achieving the intended results.
When any new master formula or method of preparation is
adopted, steps shall be taken to demonstrate its suitability for
routine processing.
Significant changes in the manufacturing process including any
changes in equipment or materials that may affect product quality
shall be validated.
18. RETURNED GOODS:

Goods which have been rejected, recalled or returned shall be
stored in adequate and segregated areas.
A Finished product returned from manufacturers own stores or
warehouse (Eg, because of spoiled or damaged labels or outer
packaging) may be relabeled or bulked for inclusion in to
subsequent batches, provided that there is no risk to the product
quality and the operation is specifically authorized and
documented.

Finished products returned from the market and which have left
the control of the manufacturer should be destroyed unless the
without doubt their quality is satisfactory; they may be
considered for relabeling or bulking for inclusion in to
subsequent batches after they have been critically assessed by
quality control personnel.
19. PRODUCT RECALLS:
There should be prompt and effective product recall system of
defective products shall be devised for timely information of all
concerned stockists, wholesalers, suppliers, up to the retail level
within the shorter period.
Recall operation shall be capable of being initiated promptly by
the licensee, so as to effectively reach at the level of each
distribution channel.
The distribution records shall be readily made available to the

persons designated for recall.
The designated person shall record a final report issued,

including reconciliation between the delivered and recovered
quantities of the product.

The recalled products shall be stored separately in secured

segregated areas.
The notification of recall should include,
- Trade names, strength, pack size and class.
- Batch number.
- Nature of the defect or reason for recall.
- Date of recall or withdrawal.
- Action to be taken.
20. TRAINING:
All production, quality assurance and store personnel and all
other personnel whose duties take them in to manufacturing
areas, should be trained in the principles of GMP and in the
practice of the tasks assigned to them.
Newly recruited personnel should receive training on the theory
and practice of GMP, and training appropriate to the duties
assigned to them.
Specific training shall be provided for personnel working in areas
of contamination, eg. Clean area or area where highly active,
toxic, infectious or sensitizing materials are handled.

The concept of quality assurance and all other measures capable

of improving its understanding and implementation should be
fully discussed during the training sessions.
Continuing training should also be given and its practical
effectiveness should be periodically assessed. Written training
programs should be available, approved by either the head of
production or the head of quality control, as appropriate. The
training records should be kept.
21. AUDIT/PAI:
Audits on all systems, procedures and operations should be
regularly conducted in order to monitor compliance with and the
effectiveness of GMP and quality assurance principles in the
various operations.
Audits may be in house or carried out by local regulatory
authorities or the regulatory authorities of countries to which
companies wish to export.
Audits should follow a pre arranged programme and include
inspection of the following
- Organizational matters and responsibilities
- Qualification and training programmers

- Compliance with hygiene requirements and entry

restrictions.
- Cleaning and disinfection programme.
- Medical checks on personnel
- Production facilities, premises, and equipment
including Q.C.
- Production operations, documentations, storage,
holding, distribution and material management
- Quality assurance aspects such as complaints,
returned goods and validation
- Suppliers of staring and packaging materials.
- Third party contractors for manufacturing,
packaging, analysis and where required distribution
of medicines.
Audit should be detailed and conducted by competent and
impartial persons from the company.
Audit reports should be made.

Productivity &amp; GMP

Загружено:

Сведения о документе

Авторское право

Доступные форматы

Поделиться этим документом

Поделиться или встроить документ

Параметры публикации

Этот документ был вам полезен?

Это неприемлемый материал?

Авторское право:

Доступные форматы

Productivity &amp; GMP

Загружено:

Авторское право:

Доступные форматы

PREFORMULATION AND PRODUCTION MANAGEMENT

PRODUCTIVITY AND GMP CONSIDERATIONS

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

Productivity may be defined as the ratio of output to input.

- are various resources like Land and building, equipment

and machinery, material, labour etc.

For management: To sell more and earn good profits.

To obtain articles at reduced price.

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

HOW TO INCREASE THE PRODUCTIVITY:

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

Productivity can be considered as increased, if more products are

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

The figure represents an economic growth process

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

a) The growth caused by an increase in production input.

increase is that the relation between output and input remains

shift of the production function and a consequent change to the

Total Productivity = Output quality and quantity

output have to be measured inclusive of both quantitative and

PRODUCTIVITY IS CREATED AND DISTRIBUTED:

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

The magnitude of the change in income distribution is directly

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

MEASURING AND INTERPRITING PARTIAL PRODUCTIVITY:

Efficiency Ratios:- which tell something

v. Managerial Control Ratio System:- these systems are

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

Quantity, Quality and

The table above is complied to compare the basic types of measurement.

OTHER ASPECTS OF PRODUCTIVITY:

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

Labour productivity: Average products of labour (average

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

Quality Control System

GOOD MANUFACTURING PRACTICE

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

GMP regulations were introduced in the form of amended schedulem in 1988.

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

The requirement is broadly stated that it casts a tremendous

It also cost a heavy burden on the industrial pharmacist, however,

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

Records of production, in-procces, final control and distribution

Nagaraja y s Dept.of Pharmaceutics

PREFORMULATION AND PRODUCTION MANAGEMENT

The premises used for manufacturing, processing, packing, labeling and

Designed, constructed, and maintained to prevent entry of insects,

Shall be well lighted, effectively ventilated, with air controlled

Nagaraja y s Dept.of Pharmaceutics

Productivity & GMP

Productivity & GMP